Hippocampal MEF2C phosphorylation mediates synaptic plasticity in lead-induced learning and memory impairments.

Lead (Pb), an ancient metallic environmental pollutant, has received widespread attention and has been strictly controlled, but current findings have found the hazards of Pb to be much higher than previously estimated. Pb exposure can lead to memory impairment. However, the underlying molecular mechanisms have not been fully elucidated.

Interplay and long-lasting effects of maternal low-level Pb, Hg, and Cd exposures on offspring cognition.

Lead (Pb), mercury (Hg), and cadmium (Cd) are prevalent and persistent environmental contaminants, causing detrimental effects on millions of individuals worldwide. Our previous research demonstrated that early-life exposure to low-level Pb, Hg, and Cd mixtures may lead to cognitive impairments. However, the association and interaction among low levels of Pb, Hg, or Cd exposure remains unclear.

Association Between Multiple Metal(loid)s Exposure and Blood Lipid Levels: Evidence from a Cross-Sectional Study of Southeastern China.

Exposure to essential and toxic metals occurs simultaneously as a mixture in real-life. However, there is no consensus regarding the effects of co-exposure to multiple metal(loid)s (designated hereafter metals) on blood lipid levels. Thus, blood concentrations of six human essential metals and five toxic metals in 720 general populations from southeastern China were simultaneously determined as a measure of exposure.

Metabolic reprogramming of glycolysis favors cartilage progenitor cells rejuvenation.

Osteoarthritis (OA), the leading cause of disability in the elderly, still lacks effective treatment due to the unelucidated mechanisms of pathogenesis and progression. In cartilage, although the solo cell type of chondrocytes is resident, cartilage progenitor cells (CPCs) are identified. Chondrocytes in cartilage mainly utilize glycolysis because of the low oxygen tension.

Co-exposure to low-dose lead, cadmium, and mercury promotes memory deficits in rats: Insights from the dynamics of dendritic spine pruning in brain development.

Lead (Pb), cadmium (Cd), and mercury (Hg) are environmentally toxic heavy metals that can be simultaneously detected at low levels in the blood of the general population. Although our previous studies have demonstrated neurodevelopmental toxicity upon co-exposure to these heavy metals at these low levels, the precise mechanisms remain largely unknown. Dendritic spines are the structural foundation of memory and undergo significant dynamic changes during development.

Association between multiple metal(loid)s exposure and renal function: a cross-sectional study from southeastern China.

In the real world, humans are exposed to multiple metal(loid)s (designated hereafter metals) that contain essential metals as well as toxic metals. Exposure to the metal mixture was assumed to be associated with renal function impairment; however, there is no consensus on available studies. Therefore, we here explored the association between multiple metals exposure and indicators of renal function in the general population from southeastern China.

Hippocampal LIMK1-mediated Structural Synaptic Plasticity in Neurobehavioral Deficits Induced by a Low-dose Heavy Metal Mixture.

Humans are commonly exposed to the representative neurotoxic heavy metals lead (Pb), cadmium (Cd), and mercury (Hg). These three substances can be detected simultaneously in the blood of the general population. We have previously shown that a low-dose mixture of these heavy metals induces rat learning and memory impairment at human exposure levels, but the pathogenic mechanism is still unclear.

Insight into the effect of a heavy metal mixture on neurological damage in rats through combined serum metabolomic and brain proteomic analyses.

The heavy metals lead (Pb), cadmium (Cd), and mercury (Hg) that cause neurocognitive impairment have been extensively studied. These elements typically do not exist alone in the environment; they are often found with other heavy metals and can enter the body through various routes, thereby impacting health. Our previous research showed that low Pb, Cd, and Hg levels cause neurobehavioral impairments in weaning and adult rats.

Cognitive outcomes caused by low-level lead, cadmium, and mercury mixture exposure at distinct phases of brain development.

Contaminated water and food are the main sources of lead, cadmium, and mercury in the human body. Long-term and low-level ingestion of these toxic heavy metals may affect brain development and cognition. However, the neurotoxic effects of exposure to lead, cadmium, and mercury mixture (Pb + Cd + Hg) at different stages of brain development are rarely elucidated.

Pregnancy and lactation mixed exposure to lead, cadmium, and mercury alters maternal-offspring single heavy metal load: A factorial design.

Environmental exposure to heavy metal mixture of lead (Pb), cadmium (Cd), and mercury (Hg) would induce hazardous health effects. However, there is a paucity of data on how exposure to heavy metal mixture alters the metabolic dynamics of individual metals. Considering that the dose plays a key role in determining the toxicity of heavy metals, we performed a factorial design with three heavy metals (Pb, Cd, and Hg) at low exposure levels.

A novel high throughput screen to identify candidate molecular networks that regulate spermatogenic stem cell functions†.

Spermatogenic regeneration is key for male fertility and relies on activities of an undifferentiated spermatogonial population. Here, a high-throughput approach with primary cultures of mouse spermatogonia was devised to rapidly predict alterations in functional capacity. Combining the platform with a large-scale RNAi screen of transcription factors, we generated a repository of new information from which pathway analysis was able to predict candidate molecular networks regulating regenerative functions.

Transcription factor-like 5 is a potential DNA- and RNA-binding protein essential for maintaining male fertility in mice.

Transcription factor-like 5 (TCFL5) is a testis-specific protein that contains the basic helix-loop-helix domain, but the in vivo functions of TCFL5 remain unknown. Herein, we generated CRISPR/Cas9-mediated knockout mice to dissect the function of TCFL5 in mouse testes. Surprisingly, we found that it was difficult to generate homozygous mice with the Tcfl5 deletion as the heterozygous males (Tcfl5+/-) were infertile.

Proper timing of a quiescence period in precursor prospermatogonia is required for stem cell pool establishment in the male germline.

The stem cell-containing undifferentiated spermatogonial population in mammals, which ensures continual sperm production, arises during development from prospermatogonial precursors. Although a period of quiescence is known to occur in prospermatogonia prior to postnatal spermatogonial transition, the importance of this has not been defined. Here, using mouse models with conditional knockout of the master cell cycle regulator Rb1 to disrupt normal timing of the quiescence period, we found that failure to initiate mitotic arrest during fetal development leads to prospermatogonial apoptosis and germline ablation.

mRBPome capture identifies the RNA-binding protein TRIM71, an essential regulator of spermatogonial differentiation.

Continual spermatogenesis relies on the actions of an undifferentiated spermatogonial population that is composed of stem cells and progenitors. Here, using mouse models, we explored the role of RNA-binding proteins (RBPs) in regulation of the biological activities of this population. Proteins bound to polyadenylated RNAs in primary cultures of undifferentiated spermatogonia were captured with oligo (dT)-conjugated beads after UV-crosslinking and profiled by proteomics (termed mRBPome capture), yielding a putative repertoire of 473 RBPs.

RyRs mediate lead-induced neurodegenerative disorders through calcium signaling pathways.

Heavy metal lead (Pb) is widely distributed in the environment and can induce neurodegeneration. Accumulating evidence has shown that ryanodine receptors (RyRs) play vital roles in neurodegenerative brain. However, whether aberrant RyRs levels contribute to Pb-induced neurodegeneration has largely remained unknown.

Lead exposure-induced cognitive impairment through RyR-modulating intracellular calcium signaling in aged rats.

Lead is widely distributed in the environment and has become a global public health issue. It is well known that lead exposure induces not only neurodevelopmental toxicity but also neurodegenerative diseases, with learning and memory impairment in the later stage. However, the molecular mechanisms remain elusive.

ECG conduction disturbances and ryanodine receptor expression levels in occupational lead exposure workers.

Objectives: A significant number of researches have evidenced that occupational lead (Pb) exposure increased risks of cardiovascular disease. However, evidences about the potential effects of Pb on the cardiac conduction system are sparse and inconclusive. Besides, ryanodine receptors (RyRs) induced dysfunction of cardiac excitation contraction coupling which is considered to be one of the mechanisms in cardiovascular diseases.

Oxidative stress in the neurodegenerative brain following lifetime exposure to lead in rats: Changes in lifespan profiles.

A large number of studies have evidenced that developmental neurotoxicity induced by lead (Pb) is related to oxidative injury. Furthermore, recent studies have found that developmental Pb exposure can induce neurodegeneration in old age. Because of the common presence of Pb in the environment, humans are exposed to this metal throughout their lifetime.

Pb modulates ryanodine receptors from the endoplasmic reticulum in rat brain.

Although the neurotoxic mechanism of lead (Pb) has been extensively studied, it is not well understood. The effects of Pb on free cytosolic calcium (Ca) concentration and calcium-regulated events have been suggested to be major mechanisms in Pb toxicity. Based on our previous findings that Pb changes calcium release through ryanodine receptors (RyRs), the modulation of endoplasmic reticulum (ER) vesicular RyRs by Pb was investigated further in the present study.

The Glial Cell-Derived Neurotrophic Factor (GDNF)-responsive Phosphoprotein Landscape Identifies Raptor Phosphorylation Required for Spermatogonial Progenitor Cell Proliferation.

Cytokine-dependent renewal of stem cells is a fundamental requisite for tissue homeostasis and regeneration. Spermatogonial progenitor cells (SPCs) including stem cells support life-long spermatogenesis and male fertility, but pivotal phosphorylation events that regulate fate decisions in SPCs remain unresolved. Here, we described a quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of SPCs following sustained stimulation with glial cell-derived neurotrophic factor (GDNF), an extrinsic factor supporting SPC proliferation.

The effect of lead exposure on expression of SIRT1 in the rat hippocampus.

Based on how the silent information regulator 2 homolog 1 (SIRT1) regulates the cyclic AMP response element binding protein (CREB), which is the molecular switch of long-term memory that maintains cognitive function, it is postulated that the impact of lead (Pb) on SIRT1 is one of the mechanisms leading to Pb-induced cognitive and learning deficits. Hence, the purpose of this study was to investigate the effect of Pb exposure on the expression of SIRT1, and the reversion effect of resveratrol, which is an activator of SIRT1. We examined the effects of maternal rat ingestion of Pb in drinking water during gestation and lactation on the expression of SIRT1 and CREB in the hippocampus of their offspring at postnatal week 3 (PNW3) and 52 (PNW52), and then reexamined these effects in offspring after intragastric administration of resveratrol for 4 weeks.

Lead-induced iron overload and attenuated effects of ferroportin 1 overexpression in PC12 cells.

Lead (Pb) neurotoxicity has received renewed interest with the growing evidence that Pb contributes to Alzheimer's disease (AD). However, the mechanism is not clear. In our previous study of long-term Pb exposure in vivo, a brain iron (Fe) overload induced by Pb was observed in elderly rats.

The effect of the hemochromatosis (HFE) genotype on lead load and iron metabolism among lead smelter workers.

Background: Both an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking.

[Effect of lead exposure on brain iron in aged rats based on the MRI].

Objective: To explore the effect of long-term lead exposure on brain iron in aged rats.

Methods: SPF female and male Sprague-Dawley rats were respectively randomly divided into three groups: control, low lead-exposed, high lead-exposed. Lead-exposed female rats drank 0.